Hyperplastic Polyposis Syndrome: Phenotypic Presentations and the Role of MBD4 and MYH
| Autor: | Shannon Cowie, Elizabeth Chow, Lara Lipton, Elly Lynch, Barbara A. Leggett, Finlay A. Macrae, Daniel D. Buchanan, Desirée du Sart, Jeremy R. Jass, Ingrid Winship, Gregor Brown, Rebecca D’Souza, Melissa A. Barker, Steven Nasioulas, Clelia Aragona, Lindy Hodgkin, Joanne P. Young |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Adenomatous polyposis coli Colorectal cancer Biopsy Polymerase Chain Reaction Gastroenterology DNA Glycosylases Familial adenomatous polyposis Germline mutation MUTYH Internal medicine medicine Humans Genetic Predisposition to Disease Alleles Germ-Line Mutation Aged Endodeoxyribonucleases Hepatology biology business.industry Microsatellite instability Colonoscopy DNA Neoplasm Middle Aged medicine.disease Pedigree Phenotype Adenomatous Polyposis Coli Hyperplastic Polyp Attenuated familial adenomatous polyposis biology.protein Female business |
| Zdroj: | Gastroenterology. 131:30-39 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2006.03.046 |
| Popis: | Background & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. Methods: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. Results: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. Conclusions: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway. |
| Databáze: | OpenAIRE |
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